tbuckley/cabot-search huggingface dataset:
Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases
Authors: Siwei Chu, Xinyi Xie, Carla Payan, Ursula Stochaj
Journal: Molecular Neurodegeneration (2023)

Abstract The AAA + ATPase valosin containing protein (VCP) is essential for cell and organ homeostasis, especially in cells of the nervous system. As part of a large network, VCP collaborates with many cofactors to ensure proteostasis under normal, stress, and disease conditions. A large number of mutations have revealed the importance of VCP for human health. In particular, VCP facilitates the dismantling of protein aggregates and the removal of dysfunctional organelles. These are critical events to prevent malfunction of the brain and other parts of the nervous system. In line with this idea, VCP mutants are linked to the onset and progression of neurodegeneration and other diseases. The intricate molecular mechanisms that connect VCP mutations to distinct brain pathologies continue to be uncovered. Emerging evidence supports the model that VCP controls cellular functions on multiple levels and in a cell type specific fashion. Accordingly, VCP mutants derail cellular homeostasis through several mechanisms that can instigate disease. Our review focuses on the association between VCP malfunction and neurodegeneration. We discuss the latest insights in the field, emphasize open questions, and speculate on the potential of VCP as a drug target for some of the most devastating forms of neurodegeneration.
Creation and Adoption of Large Language Models in Medicine
Authors: Nigam H. Shah, David Entwistle, Michael A. Pfeffer
Journal: JAMA (2023)

There is increased interest in and potential benefits from using large language models (LLMs) in medicine. However, by simply wondering how the LLMs and the applications powered by them will reshape medicine instead of getting actively involved, the agency in shaping how these tools can be used in medicine is lost.Applications powered by LLMs are increasingly used to perform medical tasks without the underlying language model being trained on medical records and without verifying their purported benefit in performing those tasks.The creation and use of LLMs in medicine need to be actively shaped by provisioning relevant training data, specifying the desired benefits, and evaluating the benefits via testing in real-world deployments.
Microfluidic Generation of Thin‐Shelled Polyethylene Glycol‐Tyramine Microgels for Non‐Invasive Delivery of Immunoprotected β‐Cells
Authors: Nuno Araújo‐Gomes, Barbara Zoetebier‐Liszka, Bas van Loo, Malin Becker, Suzanne Nijhuis, Alexandra M. Smink, Bart J. de Haan, Paul de Vos, Marcel Karperien, Jeroen Leijten
Journal: Advanced Healthcare Materials (2023)

Abstract Transplantation of microencapsulated pancreatic cells is emerging as a promising therapy to replenish β‐cell mass lost from auto‐immune nature of type I diabetes mellitus (T1DM). This strategy intends to use micrometer‐sized microgels to provide immunoprotection to transplanted cells to avoid chronic application of immunosuppression. Clinical application of encapsulation has remained elusive due to often limited production throughputs and body's immunological reactions to implanted materials. This article presents a high‐throughput fabrication of monodisperse, non‐immunogenic, non‐degradable, immunoprotective, semi‐permeable, enzymatically‐crosslinkable polyethylene glycol‐tyramine (PEG‐TA) microgels for β‐cell microencapsulation. Monodisperse β‐cell laden microgels of ≈120 µm, with a shell thickness of 20 µm are produced using an outside‐in crosslinking strategy. Microencapsulated β‐cells rapidly self‐assemble into islet‐sized spheroids. Immunoprotection of the microencapsulated is demonstrated by inability of FITC‐IgG antibodies to diffuse into cell‐laden microgels and NK‐cell inability to kill microencapsulated β‐cells. Multiplexed ELISA analysis on live blood immune reactivity confirms limited immunogenicity. Microencapsulated MIN6β1 spheroids remain glucose responsive for 28 days in vitro, and able to restore normoglycemia 5 days post‐implantation in diabetic mice without notable amounts of cell death. In short, PEG‐TA microgels effectively protect implanted cells from the host's immune system while being viable and functional, validating this strategy for the treatment of T1DM.
Effects of Cuff Size on the Accuracy of Blood Pressure Readings
Authors: Junichi Ishigami, Jeanne Charleston, Edgar R. Miller, Kunihiro Matsushita, Lawrence J. Appel, Tammy M. Brady
Journal: JAMA Internal Medicine (2023)

Importance Clinical practice guidelines recommend selecting an appropriately sized cuff based on mid-arm circumference prior to measuring blood pressure (BP). To our knowledge, the effect of miscuffing on BP measurement when using an automated BP device has not been quantified. Objective To determine the effect of using a regular BP cuff vs an appropriately sized BP cuff on automated BP readings. Design, Setting, and Participants This randomized crossover trial of community-dwelling adults with a wide range of mid-arm circumferences took place between March 16 and October 25, 2021, in Baltimore, Maryland. Participants were recruited via BP screening events at a public food market and a senior housing facility, targeted mailings to prior research participants, placement of study brochures in hypertension clinics at Johns Hopkins University, and referrals from physicians providing hypertension care to adults. Interventions Participants underwent 4 sets of triplicate BP measurements, with the initial 3 sets using an appropriate, too-small, or too-large BP cuff in random order; the fourth set of triplicate measurements was always completed with an appropriate BP cuff. Main Outcomes and Measures The primary outcome was the difference in mean BP when measured with a regular BP cuff compared with an appropriate BP cuff. The secondary outcome was the difference in BP when using too-small or too-large BP cuffs vs an appropriate BP cuff across all cuff sizes. Results were also stratified by systolic BP (≥130 mm Hg vs &amp;amp;lt;130 mm Hg) and body mass index (calculated as weight in kilograms divided by height in meters squared; ≥30 vs &amp;amp;lt;30). Results A total of 195 adults (mean [SD] age, 54 [16] years; 67 [34%] male; 132 [68%] Black; 100 [51%] with hypertension) were randomized for inclusion. Among individuals requiring a small BP cuff, use of a regular BP cuff resulted in a statistically significant lower BP reading (mean systolic BP difference, −3.6 [95% CI, −5.6 to −1.7] mm Hg). In contrast, among individuals requiring a large or extra-large BP cuff, use of a regular BP cuff resulted in a statistically significant higher BP reading (mean systolic BP difference, 4.8 [95% CI, 3.0-6.6] mm Hg and 19.5 [95% CI, 16.1-22.9] mm Hg, respectively). For the secondary outcome, BP differences with overcuffing and undercuffing by 1 and 2 cuff sizes were greater among those requiring larger BP cuffs. The results were consistent in stratified analyses by systolic BP and body mass index. Conclusions and Relevance In this randomized crossover trial, miscuffing resulted in strikingly inaccurate BP measurements. This is particularly concerning for settings where 1 regular BP cuff size is routinely used in all individuals, regardless of arm size. A renewed emphasis on individualized BP cuff selection is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04610775
Contrast-enhanced ultrasound liver imaging reporting and data system: clinical validation in a prospective multinational study in North America and Europe
Authors: Andrej Lyshchik, Corinne E. Wessner, Kristen Bradigan, John R. Eisenbrey, Flemming Forsberg, Misung Yi, Scott W. Keith, Yuko Kono, Stephanie R. Wilson, Alexandra Medellin, Shuchi K. Rodgers, Virginia Planz, Aya Kamaya, Lisa Finch, David T. Fetzer, Annalisa Berzigotti, Paul S. Sidhu, Fabio Piscaglia
Journal: Hepatology (2023)

Background and Aims: The objective of this study is to determine the diagnostic accuracy of the American College of Radiology Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System LR-5 characterization for HCC diagnosis in North American or European patients. Approach and Results: A prospective multinational cohort study was performed from January 2018 through November 2022 at 11 academic and nonacademic centers in North America and Europe. Patients at risk for HCC with at least 1 liver observation not previously treated, identified on ultrasound (US), or multiphase CT or MRI performed as a part of standard clinical care were eligible for the study. All participants were examined with CEUS of the liver within 4 weeks of CT/MRI or tissue diagnosis to characterize up to 2 liver nodules per participant using ACR CEUS Liver Imaging Reporting and Data System. Definite HCC diagnosis on the initial CT/MRI, imaging follow-up, or histology for CT/MRI-indeterminate nodules were used as reference standards. A total of 545 nodules had confirmed reference standards in 480 patients, 73.8% were HCC, 5.5% were other malignancies, and 20.7% were nonmalignant. The specificity of CEUS LR-5 for HCC was 95.1% (95% CI 90.1%–97.7%), sensitivity 62.9% (95% CI 57.9%–67.7%), positive predictive value 97.3% (95% CI 94.5%–98.7%), and negative predictive value 47.7% (95% CI 41.7%–53.8%). In addition, benign CEUS characterization (LR-1 or LR-2) had 100% specificity and 100% positive predictive value for nonmalignant liver nodules. Conclusions: CEUS Liver Imaging Reporting and Data System provides an accurate categorization of liver nodules in participants at risk for HCC.
Blocked Autophagy is Involved in Layered Double Hydroxide‐Induced Repolarization and Immune Activation in Tumor‐Associated Macrophages
Authors: Guoxin Jing, Linnan Yang, Hong Wang, Jintong Niu, Huichao Wang, Yi Gao, Youyuan Li, Bangguo Wei, Yechang Qian, Shilong Wang
Journal: Advanced Healthcare Materials (2023)

Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). The polar plasticity of TAMs makes them important targets for improving the immunosuppressive microenvironment of tumors. The previous study reveals that layered double hydroxides (LDHs) can effectively promote the polarization of TAMs from the anti-inflammatory M2 type to the pro-inflammatory M1 type. However, their mechanisms of action remain unexplored. This study reveals that LDHs composed of different cations exhibit distinct abilities to regulate the polarity of TAMs. Compared to Mg-Fe LDH, Mg-Al LDH has a stronger ability to promote the repolarization of TAMs from M2 to M1 and inhibit the formation of myeloid-derived suppressor cells (MDSCs). In addition, Mg-Al LDH restrains the growth of tumors in vivo and promotes the infiltration of activated immune cells into the TME more effectively. Interestingly, Mg-Al LDH influences the autophagy of TAMs; this negatively correlates with the pro-inflammatory ability of TAMs. Therefore, LDHs exert their polarization ability by inhibiting the autophagy of TAMs, and this mechanism might be related to the ionic composition of LDHs. This study lays the foundation for optimizing the performance of LDH-based immune adjuvants, which display excellent application prospects for tumor immunotherapy.
CD4+ T cells help myeloid-mediated killing of immune-evasive tumors
Authors: Kai Wu, Lawrence Fong
Journal: Trends in cancer (2023)

In a recent study published in Nature, Kruse et al. demonstrated an indirect tumor-killing mechanism orchestrated by a small number of CD4+ effector T cells. These CD4+ T cells can reprogram myeloid cells not just into IFNγ-induced antigen-presenting cells but also into iNOS-expressing tumoricidal effectors that can eradicate immune-evasive tumors.
The Penicillin Allergy Decision Rule—Something New for Penicillin Allergy
Authors: Allison Ramsey, S. Shahzad Mustafa
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The Krabbe Conundrum Is Really a Newborn Screening Conundrum
Authors: Beth A. Tarini, Anne E. Atkins
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Estrogen Receptor and Immune Checkpoint Inhibitors: New Partners in Lung Cancer?
Authors: Karmele Valencia, Luis M. Montuenga, Alfonso Calvo
Journal: Clinical Cancer Research (2023)

Summary The influence of sex on immunotherapy response in patients with non–small cell lung cancer (NSCLC) had been studied with no clear conclusions. An article in this issue reports that a key determinant of response is not sex but the existence of a 17β-estradiol/ERα/PDL1 signaling loop in NSCLC. This intriguing result opens new therapeutic options. See related article by Anobile et al., p. 3958
Dual Immune Checkpoint Blockade Induces Analogous Alterations in the Dysfunctional CD8+ T-cell and Activated Treg Compartment
Authors: Anne M. van der Leun, Joleen J.H. Traets, Joris L. Vos, Joris B.W. Elbers, Sanne Patiwael, Xiaohang Qiao, Mercedes Machuca-Ostos, Daniela S. Thommen, John B.A.G. Haanen, Ton N.M. Schumacher, Charlotte L. Zuur
Journal: Cancer Discovery (2023)

Abstract To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naive head and neck squamous cell carcinoma, we analyzed primary tumor immune infiltrates from responding and nonresponding patients. At baseline, a higher ratio between active (4-1BB/OX40+) and inactive regulatory CD4+ T cells was associated with immunotherapy response. Furthermore, upon therapy, this active regulatory T-cell (Treg) population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells displayed decreased expression of activity and dysfunction-related genes in responding patients, whereas in clinical nonresponders, natural killer cells showed an increased cytotoxic profile early upon treatment. These data reveal immunologic changes in response to dual PD-1/CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive Treg and CD8+ T-cell compartments in responding patients, and indicate that the presence of activated Tregs at baseline may be associated with response. Significance: In head and neck squamous cell carcinoma, neoadjuvant PD-1/CTLA4 blockade has shown substantial response rates (20%–35%). As recognition of tumor antigens by T cells appears to be a critical driver of therapy response, a better understanding of alterations in T-cell state that are associated with response and resistance is of importance. This article is featured in Selected Articles from This Issue, p. 2109
Estimating Pack-Year Eligibility for Lung Cancer Screening Using 2 Yes or No Questions
Authors: Katharine A. Rendle, Jennifer P. Steltz, Sarah Cohen, Marilyn M. Schapira, Richard C. Wender, Justin E. Bekelman, Anil Vachani
Journal: JAMA Network Open (2023)

This cross-sectional study describes the development and testing the accuracy of using 2 yes or no questions to estimate pack-year eligibility for lung cancer screening.
Dupilumab‐induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis
Authors: Fabio S. Ryser, Ayla Yalamanoglu, Alan Valaperti, Catrin Brühlmann, Tina Mauthe, Stephan Traidl, Michael B. Soyka, Urs C. Steiner
Journal: Allergy (2023)

Dupilumab, a monoclonal anti-IL-4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy.Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino-Nasal-Outcome-Test Score (SNOT-22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils.Sixty-eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT-22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM-1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down- and IL-4 upregulated in subjects with eosinophil increase.Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL-4 at baseline developed dupilumab-induced transient eosinophilia. We identified the downregulation of VCAM-1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab-induced eosinophilia.
A Nature‐Inspired Versatile Bio‐Adhesive
Authors: Mingxia Chen, Taijun Chen, Jiafan Bai, Siyuan He, Minyue Luo, Yili Zeng, Wenzhen Peng, Yuancong Zhao, Jianxin Wang, Xiangdong Zhu, Wei Zhi, Jie Weng, Kai Zhang, Xingdong Zhang
Journal: Advanced Healthcare Materials (2023)

The application of most hydrogel bio-adhesives is greatly limited due to their high swelling, low underwater adhesion, and single function. Herein, a spatial multi-level physical-chemical and bio-inspired in-situ bonding strategy is proposed, to develop a multifunctional hydrogel bio-glue using polyglutamic acid (PGA), tyramine hydrochloride (TYR), and tannic acid (TA) as precursors and 4-(4,6-dimethoxytriazine-2-yl) -4-methylmorpholine hydrochloride(DMTMM) as condensation agent, which is used for tissue adhesion, hemostasis and repair. By introducing TYR and TA into the PGA chain, it is demonstrated that not only can the strong adhesion of bio-glue to the surface of various fresh tissues and wet materials be realized through the synergistic effect of spatial multi-level physical and chemical bonding, but also this glue can be endowed with the functions of anti-oxidation and hemostasis. The excellent performance of such bio-glue in the repair of the wound, liver, and cartilage is achieved, showing a great potential in clinical application for such bio-glue. This study will open up a brand-new avenue for the development of multifunctional hydrogel biological adhesive.
Oral immunotherapy in alpha‐gal red meat allergy: Could specific <scp>IgE</scp> be a potential biomarker in monitoring management?
Authors: D. Ünal, D. Eyice‐Karabacak, A. Kutlu, S. Demir, C. Tüzer, A. F. Arslan, S. R. Işık, A. Gelincik
Journal: Allergy (2023)

Abstract Background Oral immunotherapy (OIT) is a promising treatment for food allergies. Our aim was to establish the long‐term safety and efficacy of a novel red meat (RM) OIT in galactose‐alpha‐1,3‐galactose (alpha‐gal) allergy in adults. Methods Out of 20 patients with confirmed RM allergy, five (41.66%) underwent an early OIT, seven (58.33%) underwent a delayed protocol and eight patients who were not desensitized formed the patient control group. 15 and 27 day RM OIT for early‐onset and delayed‐onset alpha‐gal allergy were administered, respectively. Desensitized patients were recommended to continue eating at least 100 g RM every day for 6 months and every other day in the following 6 months. After a year, the consumption was recommended 2/3 times in a week. Patients were followed up with skin tests with commercial beef and lamb extracts, fresh raw/cooked beef and lamb and cetuximab and also with serum alpha‐gal specific Immunoglobulin‐E (sIgE) in the first and fifth years. Results All patients who underwent OIT became tolerant to RM. During the 5 year follow‐up, the median alpha‐gal sIgE concentration gradually decreased in nine patients who consumed RM uneventfully while remained unchanged in the control group ( p = .016). In two patients, rare tick bites acted as inducers of hypersensitivity reactions with concomitant elevation of alpha‐gal sIgE concentrations whereas one patient with low follow‐up alpha‐gal sIgE concentrations consumed RM uneventfully after frequent tick bites. Conclusions Our study showed the long‐term safety and efficacy of alpha‐gal OIT. Additionally, alpha‐gal sIgE seems to be a potential biomarker to monitor OIT.
Out-of-Pocket Costs and Payer Types for Buprenorphine Among US Youth Aged 12 to 19 Years
Authors: Andrew Terranella, Gery Guy, Andrea Strahan, Christina Mikosz
Journal: JAMA Pediatrics (2023)

This cross-sectional study examines out-of-pocket costs and payer types for buprenorphine prescriptions filled for youth aged 12 to 19 years at US retail pharmacies.